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PLoS Genetics

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https://www.readbyqxmd.com/read/29337993/the-impact-of-ribosomal-interference-codon-usage-and-exit-tunnel-interactions-on-translation-elongation-rate-variation
#1
Khanh Dao Duc, Yun S Song
Previous studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongation rates from ribosome profiling data. This model-based approach allows us to quantify the extent of interference between ribosomes on the same transcript. We show that neither interference nor the distribution of slow codons is sufficient to explain the observed heterogeneity...
January 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29337989/differentially-dimensioned-furrow-formation-by-zygotic-gene-expression-and-the-mbt
#2
Yi Xie, J Todd Blankenship
Despite extensive work on the mechanisms that generate plasma membrane furrows, understanding how cells are able to dynamically regulate furrow dimensions is an unresolved question. Here, we present an in-depth characterization of furrow behaviors and their regulation in vivo during early Drosophila morphogenesis. We show that the deepening in furrow dimensions with successive nuclear cycles is largely due to the introduction of a new, rapid ingression phase (Ingression II). Blocking the midblastula transition (MBT) by suppressing zygotic transcription through pharmacological or genetic means causes the absence of Ingression II, and consequently reduces furrow dimensions...
January 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29337983/wor1-establishes-opaque-cell-fate-through-inhibition-of-the-general-co-repressor-tup1-in-candida-albicans
#3
Selma S Alkafeef, Clinton Yu, Lan Huang, Haoping Liu
The pathogenic fungus Candida albicans can undergo phenotypic switching between two heritable states: white and opaque. This phenotypic plasticity facilitates its colonization in distinct host niches. The master regulator WOR1 is exclusively expressed in opaque phase cells. Positive feedback regulation by Wor1 on the WOR1 promoter is essential for opaque formation, however the underlying mechanism of how Wor1 functions is not clear. Here, we use tandem affinity purification coupled with mass spectrometry to identify Wor1-interacting proteins...
January 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29329291/ovule-identity-mediated-by-pre-mrna-processing-in-arabidopsis
#4
Encarnación Rodríguez-Cazorla, Samanta Ortuño-Miquel, Héctor Candela, Lindsay J Bailey-Steinitz, Martin F Yanofsky, Antonio Martínez-Laborda, Juan-José Ripoll, Antonio Vera
Ovules are fundamental for plant reproduction and crop yield as they are the precursors of seeds. Therefore, ovule specification is a critical developmental program. In Arabidopsis thaliana, ovule identity is redundantly conferred by the homeotic D-class genes SHATTERPROOF1 (SHP1), SHP2 and SEEDSTICK (STK), phylogenetically related to the MADS-domain regulatory gene AGAMOUS (AG), essential in floral organ specification. Previous studies have shown that the HUA-PEP activity, comprised of a suite of RNA-binding protein (RBP) encoding genes, regulates AG pre-mRNA processing and thus flower patterning and organ identity...
January 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29329290/morc2b-is-essential-for-meiotic-progression-and-fertility
#5
Baolu Shi, Jiangyang Xue, Jian Zhou, Seth D Kasowitz, Yuanwei Zhang, Guanxiang Liang, Yongjuan Guan, Qinghua Shi, Mingxi Liu, Jiahao Sha, Xiaoyan Huang, P Jeremy Wang
The microrchidia (MORC) family proteins are chromatin-remodelling factors and function in diverse biological processes such as DNA damage response and transposon silencing. Here, we report that mouse Morc2b encodes a functional germ cell-specific member of the MORC protein family. Morc2b arose specifically in the rodent lineage through retrotransposition of Morc2a during evolution. Inactivation of Morc2b leads to meiotic arrest and sterility in both sexes. Morc2b-deficient spermatocytes and oocytes exhibit failures in chromosomal synapsis, blockades in meiotic recombination, and increased apoptosis...
January 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29329284/identification-of-an-elaborate-nk-specific-system-regulating-hla-c-expression
#6
Hongchuan Li, Martin A Ivarsson, Victoria E Walker-Sperling, Jeff Subleski, Jenna K Johnson, Paul W Wright, Mary Carrington, Niklas K Björkström, Daniel W McVicar, Stephen K Anderson
The HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells...
January 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29324767/glass-promotes-the-differentiation-of-neuronal-and-non-neuronal-cell-types-in-the-drosophila-eye
#7
Carolyn A Morrison, Hao Chen, Tiffany Cook, Stuart Brown, Jessica E Treisman
Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown. To determine whether Glass activity is limited to neuronal lineages, we compared the effects of misexpressing it in neuroblasts of the larval brain and in epithelial cells of the wing disc...
January 11, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29324765/brassinosteroids-regulate-root-growth-by-controlling-reactive-oxygen-species-homeostasis-and-dual-effect-on-ethylene-synthesis-in-arabidopsis
#8
Bingsheng Lv, Huiyu Tian, Feng Zhang, Jiajia Liu, Songchong Lu, Mingyi Bai, Chuanyou Li, Zhaojun Ding
The brassinosteroids (BRs) represent a class of phytohormones, which regulate numerous aspects of growth and development. Here, a det2-9 mutant defective in BR synthesis was identified from an EMS mutant screening for defects in root length, and was used to investigate the role of BR in root development in Arabidopsis. The det2-9 mutant displays a short-root phenotype, which is result from the reduced cell number in root meristem and decreased cell size in root maturation zone. Ethylene synthesis is highly increased in the det2-9 mutant compared with the wild type, resulting in the hyper-accumulation of ethylene and the consequent inhibition of root growth...
January 11, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29320510/adipose-tissue-atgl-modifies-the-cardiac-lipidome-in-pressure-overload-induced-left-ventricular-failure
#9
Janek Salatzki, Anna Foryst-Ludwig, Kajetan Bentele, Annelie Blumrich, Elia Smeir, Zsofia Ban, Sarah Brix, Jana Grune, Niklas Beyhoff, Robert Klopfleisch, Sebastian Dunst, Michal A Surma, Christian Klose, Michael Rothe, Frank R Heinzel, Alexander Krannich, Erin E Kershaw, Dieter Beule, P Christian Schulze, Nikolaus Marx, Ulrich Kintscher
Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysis during heart failure, we generated mice with tissue-specific deletion of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic constriction (TAC) to induce pressure-mediated cardiac failure...
January 10, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29320491/cdc73-suppresses-genome-instability-by-mediating-telomere-homeostasis
#10
Rahul V Nene, Christopher D Putnam, Bin-Zhong Li, Katarina G Nguyen, Anjana Srivatsan, Christopher S Campbell, Arshad Desai, Richard D Kolodner
Defects in the genes encoding the Paf1 complex can cause increased genome instability. Loss of Paf1, Cdc73, and, Ctr9, but not Rtf1 or Leo1, caused increased accumulation of gross chromosomal rearrangements (GCRs). Combining the cdc73Δ mutation with individual deletions of 43 other genes, including TEL1 and YKU80, which are involved in telomere maintenance, resulted in synergistic increases in GCR rates. Whole genome sequence analysis of GCRs indicated that there were reduced relative rates of GCRs mediated by de novo telomere additions and increased rates of translocations and inverted duplications in cdc73Δ single and double mutants...
January 10, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29315303/genome-wide-comparison-of-ethiopian-leishmania-donovani-strains-reveals-differences-potentially-related-to-parasite-survival
#11
Arie Zackay, James A Cotton, Mandy Sanders, Asrat Hailu, Abedelmajeed Nasereddin, Alon Warburg, Charles L Jaffe
Leishmania donovani is the main cause of visceral leishmaniasis (VL) in East Africa. Differences between northern Ethiopia/Sudan (NE) and southern Ethiopia (SE) in ecology, vectors, and patient sensitivity to drug treatment have been described, however the relationship between differences in parasite genotype between these two foci and phenotype is unknown. Whole genomic sequencing (WGS) was carried out for 41 L. donovani strains and clones from VL and VL/HIV co-infected patients in NE (n = 28) and SE (n = 13)...
January 9, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29309414/akap200-promotes-notch-stability-by-protecting-it-from-cbl-lysosome-mediated-degradation-in-drosophila-melanogaster
#12
Neeta Bala Tannan, Giovanna Collu, Ashley C Humphries, Ekatherina Serysheva, Ursula Weber, Marek Mlodzik
AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF) mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax...
January 8, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29309404/an-ichor-dependent-apical-extracellular-matrix-regulates-seamless-tube-shape-and-integrity
#13
Jeffrey B Rosa, Mark M Metzstein, Amin S Ghabrial
During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes...
January 8, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29300726/regulation-of-circadian-clock-transcriptional-output-by-clock-bmal1
#14
Alexandra J Trott, Jerome S Menet
The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output...
January 4, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29281637/cell-envelope-stress-in-mycobacteria-is-regulated-by-the-novel-signal-transduction-atpase-inir-in-response-to-trehalose
#15
Maikel Boot, Vincent J C van Winden, Marion Sparrius, Robert van de Weerd, Alexander Speer, Roy Ummels, Tige Rustad, David R Sherman, Wilbert Bitter
The cell envelope of mycobacteria is a highly unique and complex structure that is functionally equivalent to that of Gram-negative bacteria to protect the bacterial cell. Defects in the integrity or assembly of this cell envelop must be sensed to allow the induction of stress response systems. The promoter that is specifically and most strongly induced upon exposure to ethambutol and isoniazid, first line drugs that affect cell envelope biogenesis, is the iniBAC promoter. In this study, we set out to identify the regulator of the iniBAC operon in Mycobacterium marinum using an unbiased transposon mutagenesis screen in a constitutively iniBAC-expressing mutant background...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29281635/optical-silencing-of-body-wall-muscles-induces-pumping-inhibition-in-caenorhabditis-elegans
#16
Megumi Takahashi, Shin Takagi
Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activation of Arch or ACR2 with light illumination, and recovers gradually after terminating illumination...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29281629/loss-of-function-of-the-ciliopathy-protein-cc2d2a-disorganizes-the-vesicle-fusion-machinery-at-the-periciliary-membrane-and-indirectly-affects-rab8-trafficking-in-zebrafish-photoreceptors
#17
Irene Ojeda Naharros, Matthias Gesemann, José M Mateos, Gery Barmettler, Austin Forbes, Urs Ziegler, Stephan C F Neuhauss, Ruxandra Bachmann-Gagescu
Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29281627/an-essential-regulatory-function-of-the-dnak-chaperone-dictates-the-decision-between-proliferation-and-maintenance-in-caulobacter-crescentus
#18
Frederic D Schramm, Kristina Heinrich, Marietta Thüring, Jörg Bernhardt, Kristina Jonas
Hsp70 chaperones are well known for their important functions in maintaining protein homeostasis during thermal stress conditions. In many bacteria the Hsp70 homolog DnaK is also required for growth in the absence of stress. The molecular reasons underlying Hsp70 essentiality remain in most cases unclear. Here, we demonstrate that DnaK is essential in the α-proteobacterium Caulobacter crescentus due to its regulatory function in gene expression. Using a suppressor screen we identified mutations that allow growth in the absence of DnaK...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29281626/integrated-rare-variant-based-risk-gene-prioritization-in-disease-case-control-sequencing-studies
#19
Jhih-Rong Lin, Quanwei Zhang, Ying Cai, Bernice E Morrow, Zhengdong D Zhang
Rare variants of major effect play an important role in human complex diseases and can be discovered by sequencing-based genome-wide association studies. Here, we introduce an integrated approach that combines the rare variant association test with gene network and phenotype information to identify risk genes implicated by rare variants for human complex diseases. Our data integration method follows a 'discovery-driven' strategy without relying on prior knowledge about the disease and thus maintains the unbiased character of genome-wide association studies...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29281624/the-smc5-6-complex-regulates-the-yeast-mph1-helicase-at-rna-dna-hybrid-mediated-dna-damage
#20
Juan Lafuente-Barquero, Sarah Luke-Glaser, Marco Graf, Sonia Silva, Belén Gómez-González, Arianna Lockhart, Michael Lisby, Andrés Aguilera, Brian Luke
RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci...
December 27, 2017: PLoS Genetics
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